Cross-regulation between Notch and p63 in keratinocyte commitment to differentiation

Bach Cuc Nguyen, Karine Lefort, Anna Mandinova, Dario Antonini, Vikram Devgan, Giusy Della Gatta, Maranke I. Koster, Zhuo Zhang, Jian Wang, Alice Tommasi Di Vignano, Jan Kitajewski, Giovanna Chiorino, Dennis R. Roop, Caterina Missero, G. Paolo Dotto

Research output: Contribution to journalArticle

Abstract

Notch signaling promotes commitment of keratinocytes to differentiation and suppresses tumorigenesis. p63, a p53 family member, has been implicated in establishment of the keratinocyte cell fate and/or maintenance of epithelial self-renewal. Here we show that p63 expression is suppressed by Notch1 activation in both mouse and human keratinocytes through a mechanism independent of cell cycle withdrawal and requiring down-modulation of selected interferon-responsive genes, including IRF7 and/or IRF3. In turn, elevated p63 expression counteracts the ability of Notch1 to restrict growth and promote differentiation. p63 functions as a selective modulator of Notch1-dependent transcription and function, with the Hes-1 gene as one of its direct negative targets. Thus, a complex cross-talk between Notch and p63 is involved in the balance between keratinocyte self-renewal and differentiation.

Original languageEnglish
Pages (from-to)1028-1042
Number of pages15
JournalGenes and Development
Volume20
Issue number8
DOIs
Publication statusPublished - Apr 15 2006

Keywords

  • HES/HERP family members
  • Interferon-responsive genes
  • Keratinocyte
  • Notch
  • p63
  • Stem cells

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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  • Cite this

    Nguyen, B. C., Lefort, K., Mandinova, A., Antonini, D., Devgan, V., Gatta, G. D., Koster, M. I., Zhang, Z., Wang, J., Di Vignano, A. T., Kitajewski, J., Chiorino, G., Roop, D. R., Missero, C., & Dotto, G. P. (2006). Cross-regulation between Notch and p63 in keratinocyte commitment to differentiation. Genes and Development, 20(8), 1028-1042. https://doi.org/10.1101/gad.1406006